Fixed Versus Variable Dosing of Prothrombin Complex Concentrate in Vitamin K Antagonist-Related Intracranial Hemorrhage: A Retrospective Analysis

Abstract

BackgroundMillions of patients receive vitamin K antagonist (VKA) therapy worldwide. Annually 0.2–1 % of all VKA users develops an intracranial hemorrhage (ICH). Prothrombin complex concentrate (PCC) is administered to restore the INR ≤ 1.5 in an attempt to limit hematoma growth. In order to facilitate PCC dosing, our hospital recently changed from a variable dose based on bodyweight, baseline- and target-INR, to a fixed 1000 IU fIX PCC dosing protocol for ICH.MethodsIn a before and after design, we compared successful achievement of an INR ≤ 1.5 with a fixed dosing strategy versus the variable dosing strategy of PCC in patients presenting with intracranial bleeding complications of VKA. Data of the two cohorts of patients were retrospectively collected from medical records.ResultsA median dosage of 1750 IU was given per patient in the variable dose group (n = 25) versus 1000 IU in the fixed dose group (n = 28). In the intention-to-treat analysis, 96 % achieved an INR ≤ 1.5 after an initial dose in the variable dose cohort compared to 68 % in the fixed dose cohort (p = 0.01). An additional dose was given in 2 (8 %) versus 9 (32 %) patients, respectively (p = 0.04). The median door-to-PCC-order time was 42 versus 32 min (p = 0.37) and the door-to-needle time was 81, respectively 60 min (p = 0.42).ConclusionThe fixed dose protocol necessitates additional PCC infusions more frequently to achieve a target INR ≤ 1.5. Door-to-order and door-to-needle time were shorter but, in this small cohort, not significantly so. The effect on clinical outcome remains unknown.

Prothrombin Complex Concentrate for Vitamin K Antagonist-Associated Intracranial Hemorrhage ― Global Evidence and the Japanese Perspective ―

“…58- 60 Abdoellakhan and colleagues 58 retrospectively assessed the effect of a change in protocol at their center in the Netherlands. A variable 4F-PCC dosing regimen (based on body weight, initial and target INR, according to manufacturer's instructions; median dose 23 IU/kg) was compared modified Rankin Scale (mRS) and extended Glasgow Outcome Scale scores at day 90), the study was not powered for these endpoints.…”

Randomised controlled trial protocol to evaluate a fixed dose prothrombin complex concentrate against the variable dose in vitamin K antagonist related bleeding (PROPER3)

“…The exclusion of intracranial bleeds in the current study is based on the lack of pilot data supporting the use of a fixed dose. 19 …”

Fixed‐Dose Four‐Factor Prothrombin Complex Concentrate for Vitamin K Antagonist Reversal: Does One Dose Fit All?

“…Although target INR < 1.5 was successfully reached in 71.8% of patients, poor clinical response and mortality were high. Another study also evaluated a fixed 1000‐IU dose of 4F‐PCC (Cofact) for reversal of VKA‐associated ICH with a retrospective, before/after cohort design in 53 patients comparing fixed dosing versus variable dosing (median 1750 IU) based on manufacturer recommendations . Attainment of target INR ≤ 1.5 occurred in a significantly lower proportion of patients in the fixed‐dose group compared to the variable‐dose group (68% vs 96%, p=0.013), and repeat dosing was required more often (32% vs 8%, p=0.043, respectively).…”